Monolayers of cultured fibroblasts from normal human subjects bind 125I labeled low density lipoproteins with high affinity and specificity. High affinity binding of similar magnitude was not observed in cells from 5 unrelated subjects with the homozygous form of familial hypercholesterolemia. In normal cells incubated at 37°, the binding sites were saturated at a low density lipoprotein concentration of 20 μg/ml. A maximum of approximately 250,000 molecules could be bound to each cell. Whole serum and very low density lipoproteins displaced 125I labeled low density lipoproteins from the binding sites, but high density lipoproteins, the lipoprotein deficient fraction of serum, and abetalipoproteinemic serum did not. This binding appears to be a required step in the process by which low density lipoproteins normally suppress the synthesis of 3 hydroxy 3 methyl glutaryl coenzyme A reductase, the rate controlling enzyme in cholesterol biosynthesis. The demonstration of a defect in binding of low density lipoproteins to cells from subjects with the homozygous form of familial hypercholesterolemia appears to explain the previously reported failure of lipoproteins to suppress the synthesis of this enzyme and hence may account for the overproduction of cholesterol that occurs in these cultured cells.
|Original language||English (US)|
|Number of pages||5|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - Jan 1 1974|
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